Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis

Hofmann, Sylvia; Franke, André; Fischer, Annegret; Jacobs, Gunnar; Nothnagel, Michael; Gaede, Karoline I.; Schürmann, Manfred; Müller–Quernheim, Joachim; Krawczak, Michael; Rosenstiel, Philip; Schreiber, Stefan

doi:10.1038/ng.198

Cited by 243 publications

(198 citation statements)

References 26 publications

Supporting

Mentioning

176

Contrasting

Unclassified

Order By: Relevance

“…The frequency of ANXA11 rs1049550*T allele was significantly lower in our (Czech) patients with sarcoidosis (35%) compared with the frequency observed in the control group (42%, P ¼ 0.04, odds ratio ¼ 0.77, Table 1). In concordance with study in German sarcoidosis patients, 6 the 'protective' effect of ANXA11*T allele increased with the number of its copies in the genotype (gene-dose effect) (Figure 1).…”

Section: Resultssupporting

confidence: 87%

“…12,13 However, no relationship between ANXA11 gene variants and any immune-mediated disease was revealed nor suggested before it was nominated by the first GWAS in sarcoidosis. 6 In the present study we replicated contribution of ANXA11 rs1049550 SNP to the genetic susceptibility to sarcoidosis. Particularly, the ANXA11 rs1049550*T variant was associated with protection from sarcoidosis and the level of protection has been shown to depend on the number T alleles in the genotype (gene-dose effect).…”

Section: Resultssupporting

confidence: 77%

“…5 The first genome-wide association study (GWAS) in sarcoidosis conducted in the German population has recently revealed an association of the variants in the ANXA11 (annexin A11) gene with susceptibility to sarcoidosis. 6 This association has recently been supported by another report from the same population. 7 The aim of this work was to replicate the association of ANXA11 single nucleotide polymorphism (SNP) rs1049550 (R230C), a key coding variant associated with sarcoidosis in GWAS.…”

Section: Introductionsupporting

confidence: 59%

“…Association of the ANXA11 rs1049550 SNP with clinical phenotypes of sarcoidosis In addition to replication of the principal findings from the GWAS, 6 we investigated also whether the ANXA11 rs1049550 SNP might be associated with particular clinical phenotypes of sarcoidosis, namely the chest radiographic (CXR) stages of the disease and presence of the LS. Importantly, ANXA11*T allele was less frequent in patients with the infiltration of lung parenchyma (CXR stages II-IV) compared with the patients with isolated hilar lymphadenopathy (CXR stage I, P ¼ 0.01, Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…7 The aim of this work was to replicate the association of ANXA11 single nucleotide polymorphism (SNP) rs1049550 (R230C), a key coding variant associated with sarcoidosis in GWAS. 6 We wondered also whether this ANXA11 SNP might be related to the clinical manifestation of sarcoidosis. Further, the local mRNA expression of ANXA11 gene in bronchoalveolar lavage (BAL) cells was investigated in patients with sarcoidosis with distinct ANXA11 rs1049550 SNP genotypes to provide further functional data.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Functional variant ANXA11 R230C: true marker of protection and candidate disease modifier in sarcoidosis

et al. 2011

View full text Add to dashboard Cite

Section: Resultssupporting

confidence: 87%

Section: Resultssupporting

confidence: 77%

Section: Introductionsupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Functional variant ANXA11 R230C: true marker of protection and candidate disease modifier in sarcoidosis

et al. 2011

View full text Add to dashboard Cite

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

et al. 2015

View full text Add to dashboard Cite

IMPORTANCE Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy.OBJECTIVE To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. DESIGN, SETTING, AND PARTICIPANTSIn a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. MAIN OUTCOMES AND MEASURESSignificantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05.RESULTS Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues.CONCLUSIONS AND RELEVANCE Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.

show abstract

Molecular Genetics of Sarcoidosis

Paul

Iannuzzi

2012

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Sarcoidosis is a systemic inflammatory disorder characterised by the presence of noncaseating granulomas. The aetiology of sarcoidosis remains unknown. Although any organ system can be involved, the common cause of morbidity and mortality occurs from involvement of the lung, heart and nervous system. There has been extensive research, directed on the identification of candidate genes (both HLA and non‐HLA) that lead to dysregulation of the T‐cell response in sarcoidosis. However, most of these reported associations between these genes and susceptibility to sarcoidosis have not been replicated. Advances in genomics and proteomics, in concert with emerging technologies, are expected to provide further insight into pathogenesis and disease risk. Key Concepts: Sarcoidosis is a systemic inflammatory disorder characterised by the presence of noncaseating granulomas of unknown aetiology. Studies have revealed many candidate genes (both HLA and non‐HLA) that lead to dysregulation of the T‐cell response in sarcoidosis. A new strategy is to subgroup patients into distinct clinical phenotypes to help identify genes of importance for the disease. Gene expression profiling in BAL fluid and blood performed at the time of presentation may help to better predict disease resolution or progression. Advances in genomics and proteomics, in concert with emerging technologies, are expected to provide further insight into pathogenesis and disease risk.

show abstract

Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis

Cited by 243 publications

References 26 publications

Functional variant ANXA11 R230C: true marker of protection and candidate disease modifier in sarcoidosis

Functional variant ANXA11 R230C: true marker of protection and candidate disease modifier in sarcoidosis

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

Molecular Genetics of Sarcoidosis

Contact Info

Product

Resources

About